A comparison between the negative inotropic action of various antiarrhythmic drugs and their influence on calcium movements in heart muscle

The influence of quinidine, lidocaine, (+)- and (±)-propranolol, l-(+)- and d-(–)-INPEA and (±)-alprenolol on contractile force and transmembraneous calcium exchange was studied in beating guinea-pig atria (3Hz) and in resting left auricles. Quinidine and lidocaine (5 × 10−5m) reduced the contractile force by approximately 34 and 19%, respectively. Both drugs diminished the Ca2+ flux during excitation without affecting the exchangeable fraction at equilibrium or the total Ca2+ content. In resting auricles both drugs did not influence the passive Ca permeability whatsoever. (+)- or (±)-Propranolol and alprenolol (5 × 10−5m) depressed the contractile force by approximately 60 and 33 % of the initial value, INPEA (both isomers) hardly showed negative inotropic properties. None of these β-adrenoceptor blocking agents significantly affected the calcium fluxes or the total Ca2+ content, either in beating atria or in resting auricles. The negative inotropic action of quinidine and lidocaine might be explained at least in part by the reduced rate of transmembraneous calcium exchange. For the β-adrenoceptor blocking compounds such a mechanism cannot be the cause of their depression of cardiac contractile force. It is suggested that the expression “quinidine like” effect is not adequate for the general description of the negative inotropic side effect of most β-adrenoceptor blocking and related drugs.